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Extracorporeal Membrane OxygenationTITRENCT05405426

Trial of Indication-Based Transfusion of Red Blood Cells in ECMO

A study testing Red blood cell transfusion in people with Extracorporeal Membrane Oxygenation and Red Blood Cell Transfusion, run by Boston Children's Hospital at 22 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

TITRE - Trial of Indication-based Transfusion of Red Blood Cells in ECMO, is a multicenter, prospective, randomized clinical trial. The overarching goal of TITRE is to determine whether restricting red blood cell (RBC) transfusion according to an indication-based strategy for those with bleeding and/or deficit of… Read more about this study

Who is it for?
Ages 0 days to 6 years
What is being tested?
Red blood cell transfusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
228 participants
Where
22 sitesin 3 countries
Study dates
14 Apr 2023to Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 days to 6 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Age < 6 year at ECMO cannulation
  • Veno-arterial (VA) mode of ECMO
  • First ECMO run during the index hospitalization

Who cannot join

  • Gestationally-corrected age < 37 weeks at the time of ECMO cannulation
  • Veno-venous (VV) mode of ECMO
  • Patients initially started on VV-ECMO and then transitioned to VA ECMO > 18 hours after ECMO cannulation
  • ECMO used for procedural support (ECMO deployed and decannulated in procedural area with no ICU ECMO care) or ECMO duration expected to be < 24 h
  • Limitation of care in place or being discussed
  • Congenital bleeding disorders
Show all 13Show fewer
  • Hemoglobinopathies
  • Primary Residence outside country of enrollment
  • Concurrent participation in a separate interventional trial that has potential to impact neurodevelopment status of patient. (note that observational non-interventional studies do not qualify the patient for exclusion). This includes a patient already enrolled in TITRE
  • Lack of access to medical records required for calculation of pre-ECMO pSOFA score due to cannulation for ECMO at a non-trial center.
  • Randomization not possible within 36 h following ECMO cannulation (e.g., due to staffing or delays related to communication with participant family)
  • Planned transition to ventricular assist device (VAD) within 48 hours of commencing ECMO.
  • Clinically documented indication for a Red Blood Cell transfusion threshold that differs from the center-specific transfusion threshold (e.g., oncological treatment that limits donor exposure).

Trial locations and contacts

22 sites in 3 countries.

22 sites in 3 countries

United States20 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30322

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • MUSC Shawn Jenkins Children's Hospital

    Charleston, South Carolina, 29425

  • Lurie Children's Hospital

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Children's Health Dallas University of Texas Southwestern

    Dallas, Texas, 75235

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • Inova Children's Hospital

    Falls Church, Virginia, 22042

  • Texas Children's Hospital - Baylor College of Medicine

    Houston, Texas, 77030

  • Riley Children's Hospital

    Indianapolis, Indiana, 46202

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Monroe Carell Jr. Children's Hospital at Vanderbilt

    Nashville, Tennessee, 37232

  • Lucile Packard Children's Hospital

    Palo Alto, California, 94304

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • Primary Children's Hospital

    Salt Lake City, Utah, 84132

  • Seattle Children's Hospital

    Seattle, Washington, 98105

Other trials in United States

Australia1 site

  • The Children's Hospital at Westmead

    Westmead, New South Wales

Other trials in Australia

Canada1 site

  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: TITRE: Trial of Indication-Based Transfusion of Red Blood Cells in ECMO

TITRE - Trial of Indication-based Transfusion of Red Blood Cells in ECMO, is a multicenter, prospective, randomized clinical trial. The overarching goal of TITRE is to determine whether restricting red blood cell (RBC) transfusion according to an indication-based strategy for those with bleeding and/or deficit of tissue oxygen delivery, compared with transfusion based on center-specific hemoglobin or hematocrit thresholds, can reduce organ dysfunction and improve later neurodevelopment in critically ill children receiving Extracorporeal Membrane Oxygenation (ECMO) support.

Read the detailed description

Observational studies of children on ECMO have shown an association between large-volume RBC transfusion and mortality. However, the hematocrit (or hemoglobin) level at which optimal tissue oxygen delivery occurs is unknown. TITRE - Trial of Indication-based Transfusion of Red Blood Cells in ECMO, is a prospective, randomized clinical trial to be conducted at 22 study sites. The overarching goal of TITRE is to determine whether restricting RBC transfusion according to an indication-based strategy for those with bleeding and/or deficit of tissue oxygen delivery, compared with transfusion based on center-specific hemoglobin or hematocrit thresholds, can reduce organ dysfunction and improve later neurodevelopment in critically ill children receiving ECMO support.

Aim 1: To test whether children < 6 years of age on ECMO support who are randomized to a strategy of indication-based versus center-specific threshold-based RBC transfusion will have greater improvement in organ function.

Aim 2: To test whether survivors among children age < 6 years on ECMO support who are randomized to indication-based compared to center-specific threshold-based RBC transfusion will have better neurodevelopmental outcomes and health-related QOL at one year post-randomization.

Key design features include: Randomization stratified by patient age (neonate:

=< 28d vs. non-neonate) and by diagnosis (CHD vs. other diagnosis); and a target sample size of 240 patients. Endpoints will be evaluated during ECMO, at hospital discharge, and at 3, 6, 9, and 12 months. To ensure trial integrity, the primary outcome (pSOFA: Pediatric Sequential Organ Failure Assessment score) will be adjudicated by an independent committee and neurodevelopmental assessments will be blinded.

Being tested
Red blood cell transfusion
Keywords
pediatric, children, ECMO, transfusion, neurodevelopment, TITRE
Medical subject headings
Multiple Organ Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Red blood cell transfusionOther

    The intervention is a strategy for when red blood cell transfusion will be administered (see description of Arms). However, volume of RBC transfused in the two arms is not specified by this study. Red blood cell transfusion strategy for ECMO weaning and decannulation is not specified by this study. Red blood cell transfusion after ECMO decannulation is not specified by this study.

Study groups in NCT05405426
Study groupRoleWhat they receive
Indication-based red blood cell transfusion strategyActive comparatorRed blood cell transfusion will occur if the center-specific hemoglobin/hematocrit threshold for transfusion is met AND at least one of the following conditions is present: a) moderate or severe bleeding; b) reduced tissue oxygen delivery, defined as serum lactate >5 mmol/L or 2 serum lactate levels > 3 mmol/L measured 2 hours apart; or c) hemoglobin < 8 g/dL or hematocrit < 25%, except for neonates (age =< 28 d) and children with single ventricle congenital heart disease (age < 1 y) RBC transfusion for hemoglobin < 10g/dL or hematocrit <30% is allowed.
Receives: Other: Red blood cell transfusion
Center-specific hemoglobin/hematocrit threshold-based red blood cell transfusion strategyOtherRed blood cell transfusion will occur according to each study center's standard of care strategy, typically based on a particular hemoglobin threshold or hematocrit threshold. When hemoglobin or hematocrit decrease to the threshold, red blood cell transfusion is administered.
Receives: Other: Red blood cell transfusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Baseline-adjusted change in pSOFA (pediatric Sequential Organ Failure Assessment) score

    The pSOFA score ranges from 0 (no organ dysfunction) through 24 (severe dysfunction in all 6 organs assessed). If death occurs during ECMO within 30 days, a score of 24 is assigned.

    Measured: At randomization and at 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)

  2. Bayley Infant Scales of Development, 4th edition (Bayley-4)

    Scales for Cognitive, Language (Expressive and Receptive), Motor (Gross and Fine), and Social-Emotional. For ages 16 days to 42 months. Composite score range is 40 to 160.

    Higher scores indicate better performance.

    Measured: One year post-randomization (+/- 2 mo)

  3. Wechsler Preschool and Primary Scale of Intelligence (WPPSI - IV)

    Index scores include Verbal Comprehension, Visual Spatial, Working Memory, and Full Scale Intelligence Quotient (IQ). Score range is 40 to 160. Higher scores indicate better performance.

    Measured: One year post-randomization (+/-2 mo)

Secondary outcomes (27)

  1. Mixed venous oxygen saturation

    Oxygen content of blood that returns to the heart after meeting tissue needs

    Measured: Daily AM (6 AM - 12 AM), during ECMO (up to 30 days post-randomization, whichever is earlier)

  2. Total volume of blood products administered

    Packed RBC and whole blood, cryoprecipitate, plasma, platelets

    Measured: 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)

  3. Presence vs. absence of hospital-acquired blood stream Infection

    Hospital-acquired blood stream infection that is not present or incubating at the time of admission to hospital

    Measured: 30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)

  4. Daily renal function

    Serum creatinine, blood urea nitrogen (BUN)

    Measured: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)

  5. Acute kidney injury > stage 2

    Kidney Disease Improving Global Outcomes (KDIGO) definition

    Measured: 30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)

  6. Number of ECMO circuit component replacements

    Replacement of oxygenator and/or pump

    Measured: At 30 days post-randomization

  7. Presence vs. absence of hemolysis

    According to plasma hemoglobin values

    Measured: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)

  8. All-cause mortality

    Death from any cause

    Measured: 30 days, in-hospital, and 1 year post-randomization

  9. Discharge location

    Home vs. rehabilitation facility

    Measured: At time of hospital discharge (assessed up to 1 year)

  10. Adaptive Behavior Assessment System-3 (ABAS-3)

    Composite scores for overall adaptive functioning (General Adaptive Composite, GAC), Conceptual, Social and Practical domains as well as nine subscales. Higher score indicates better behavior.

    Measured: 1 year post-randomization (+/- 2 mo)

  11. Child Behavior Checklist (CBCL)

    Parent-report; child minimum age 1.5 years. Higher score indicates worse behavior.

    Measured: 1 year post-randomization (+/- 2 mo)

  12. Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0)

    Parent-report; child minimum age 2.0 years. Higher score indicates better quality of life.

    Measured: 9 months post-randomization (+/- 1 mo)

  13. Pediatric Quality of Life Inventory Cardiac Module

    Parent-report; child minimum age 2.0 years. To be completed for participants with a congenital heart disease diagnosis. Higher score indicates better quality of life.

    Measured: 9 months post-randomization (+/- 1 mo)

  14. Number of Donor Exposures

    Number of Donor Exposures for RBC transfusion

    Measured: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)

  15. Recannulation for ECMO < 48 hours and < 72 hours after decannulation

    No: of patients recannulated for ECMO within 48 hours and 72 hours post-decannulation

    Measured: From ECMO decannulation hour to 72 hours following ECMO decannulation

  16. ECMO duration

    ECMO duration in hours: Time period from ECMO cannulation to first successful ECMO decannulation in hours. Time accrued during ECMO for additional ECMO runs (i.e. those cannulated within 36 hours following first decannulation) will be included as total ECMO duration

    Measured: During Hospitalization: From ECMO cannulation to ECMO decannulation, death, transition to Ventricular Assist Device (VAD) or 365 days post-randomization, whichever is earliest

  17. Duration of mechanical ventilation post-randomization

    Duration of mechanical ventilation post-randomization in hours: Randomization to first successful extubation from mechanical ventilation hours; for patients with tracheostomy that require mechanical ventilatory support at the time of ICU discharge: time of ICU discharge to compute mechanical ventilation duration.

    Measured: During Hospitalization: From Randomization to Extubation from Mechanical Ventilation, death, hospital discharge, or 365 days post-randomization, whichever is earliest

  18. Occurrence of Seizures

    Occurrence of electroencephalographic evidence of seizure prior to hospital discharge or within 90 d post randomization, whichever is earliest

    Measured: Randomization to Hospital Discharge or 90 days post-randomization, whichever is earliest

  19. Stroke or Intracranial Hemorrhage during ECMO

    Occurrence of brain infarction, intracranial hemorrhage, or ischemic injury during ECMO (composite) confirmed using head ultrasound and Computed Tomography (CT) during ECMO

    Measured: Time of ECMO cannulation to ECMO decannulation, death or 30 days post-randomization, whichever occurs first

  20. Stroke or Intracranial Hemorrhage prior to Hospital Discharge

    Proportion of patients with brain infarction, intracranial hemorrhage, or ischemic injury (composite) confirmed using head ultrasound, CT, or Magnetic Resonance Imaging (MRI) prior to hospital discharge or within 90 d post randomization, whichever is earliest

    Measured: ECMO cannulation to 90 days post-randomization or hospital discharge, whichever occurs first

  21. Pediatric Overall Performance Category (POPC)

    Pediatric Overall Performance (POPC; score range 0 to 6; Unit: categories on a scale; value: lower is better) at Hospital Discharge, 3, 6, 9, 12 months post-randomization.

    Measured: Randomization to study completion (completion of 12 month neurodevelopment assessment)

  22. Functional Status Score (FSS)

    Functional Status Score (FSS; score range 6 to 30; Unit: numerical value on a scale; lower is better) at hospital discharge, 3, 6, 9, 12 months post-randomization

    Measured: Randomization to study completion (completion of 12 month neurodevelopment assessment)

  23. ICU Length of Stay among survivors during index hospitalization

    Duration of hospitalization in the ICU among survivors in days during index hospitalization. For ICU readmissions only the only days in the first 2 ICU readmissions will be included

    Measured: ICU Admission to ICU discharge, death or 365 post-randomization, whichever occurs first

  24. Hospital length of stay among survivors during index hospitalization

    Duration of hospitalization among survivors in days during index hospitalization

    Measured: Hospital Admission to discharge death, or 365 days post-randomization, whichever occurs first

  25. Pediatric Cerebral Performance Category (PCPC)

    Pediatric Cerebral Performance Category (POPC; score range 0 to 6; Unit: categories on a scale, lower is better) at Hospital Discharge, 3, 6, 9, 12 months post-randomization.

    Measured: Randomization to study completion (completion of 12 month neurodevelopment assessment)

  26. Number of ICU admissions prior to discharge from index hospitalization among survivors

    Number of ICU admissions during index hospitalization. ICU admissions are defined as number of ICU admissions following discharge from the first ICU admission.

    Measured: Index ICU discharge to Hospital discharge or 365 days post-randomization, whichever occurs first

  27. Proportion of ECMO days meeting moderate - severe bleeding criteria

    Number of days meeting criteria for moderate or severe bleeding during ECMO

    Measured: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2022
  2. Study start14 Apr 2023
  3. Primary completionOct 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Model description
Two independent study arms will be used: indication-based red blood cell transfusion strategy vs. a center-specific standard of care hemoglobin/hematocrit threshold-based red blood cell transfusion strategy
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
228 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05405426
Sponsor's protocol ID
W81XWH-22-1-0301
Acronym
TITRE
Status last verified
Jul 2026
First submitted
2 May 2022
Last updated
2 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Red blood cell transfusion in people with Extracorporeal Membrane Oxygenation and Red Blood Cell Transfusion, run by Boston Children's Hospital at 22 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Baseline-adjusted change in pSOFA (pediatric Sequential Organ Failure Assessment) score (time frame: At randomization and at 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05405426.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.

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